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Early extracellular matrix changes are associated with later development of bronchiolitis obliterans syndrome after lung transplantation

机译：早期细胞外基质变化与肺移植后闭塞性细支气管炎综合征的后期发展有关

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BACKGROUND: Chronic lung allograft dysfunction in the form of bronchiolitis obliterans syndrome (BOS) is the main cause of death beyond 1-year post-lung transplantation. The disease-initiating triggers as well as the molecular changes leading to fibrotic alterations in the transplanted lung are largely unknown. The aim of this study was to identify potential early changes in the extracellular matrix (ECM) in different compartments of the transplanted lung prior to the development of BOS.METHODS: Transbronchial biopsies from a cohort of 58 lung transplantation patients at the Copenhagen University hospital between 2005 and 2006, with or without development of BOS in a 5-year follow-up, were obtained 3 and 12 months after transplantation. Biopsies were assessed for total collagen, collagen type IV and biglycan in the alveolar and small airway compartments using Masson's Trichrome staining and immunohistochemistry.RESULTS: A time-specific and compartment-specific pattern of ECM changes was detected. Alveolar total collagen (p=0.0190) and small airway biglycan (p=0.0199) increased between 3 and 12 months after transplantation in patients developing BOS, while collagen type IV (p=0.0124) increased in patients without BOS. Patients with early-onset BOS mirrored this increase. Patients developing grade 3 BOS showed distinct ECM changes already at 3 months. Patients with BOS with treated acute rejections displayed reduced alveolar total collagen (p=0.0501) and small airway biglycan (p=0.0485) at 3 months.CONCLUSIONS: Patients with future BOS displayed distinct ECM changes compared with patients without BOS. Our data indicate an involvement of alveolar and small airway compartments in post-transplantation changes in the development of BOS.
机译：背景：以闭塞性细支气管炎综合征（BOS）形式出现的慢性肺同种异体功能障碍是肺移植后1年以上的主要死亡原因。引起疾病的触发因素以及导致移植肺中纤维化改变的分子变化在很大程度上尚不清楚。这项研究的目的是在BOS发生之前确定移植肺不同腔室中细胞外基质（ECM）的潜在早期变化。方法：哥本哈根大学医院58例肺移植患者队列中的经支气管活检在移植后3个月和12个月，获得了2005年和2006年的5年随访结果，无论有无BOS发生。使用Masson的Trichrome染色和免疫组织化学方法，对活检组织的肺泡和小气道隔室中的总胶原蛋白，IV型胶原蛋白和双糖链蛋白进行了评估。结果：检测到了ECM变化的时间特异性和隔室特异性模式。发生BOS的患者在移植后3至12个月内，肺泡总胶原（p = 0.0190）和小气道双糖聚糖（p = 0.0199）增加，而没有BOS的患者IV型胶原（p = 0.0124）增加。 BOS早期发作的患者反映了这种增加。进展为3 BOS的患者在3个月时已经显示出明显的ECM变化。经过治疗的急性排斥反应的BOS患者在3个月时显示出肺泡总胶原蛋白减少（p = 0.0501）和小气道双链聚糖（p = 0.0485）。结论：与没有BOS的患者相比，未来BOS的患者表现出明显的ECM变化。我们的数据表明，肺泡和小气道室参与了BOS移植后移植的变化。

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